Physiological aging is characterized by decreased responses to stress. This project examined the effect of aging on the cellular response to heat stress at the molecular level. The effect of aging on the heat-induced expression of the heat shock protein HSP 70 was studied in skin and lung fibroblast cultures from young (5 months) and aged (24 months) male Wistar rats. The kinetics of the heat shock response were found to be similar in the two age groups but cells from aged animals showed significantly lower levels of heat-induced HSP 70 MRNA compared to those from younger animals. Experiments analyzing HSP 70 protein showed a correlative decrease in HSP 70 protein in cells from aged animals. The response was specific for HSP 70 as other heat shock proteins were unaffected. Additional experiments with freshly excised lung tissue showed a similar age-related decline in the heat-induced expression of HSP 70. While their name is derived from the response to heat stress, the heat shock proteins are induced by a variety of cellular stresses and are presumed to play a role in protecting cells against these stresses. Our studies demonstrating an age-related reduction in HSP 70 expression following heat stress in fresh lung tissue and cultured cells suggest that these protective roles of HSP 70 may be impaired with aging.